PD-L1 and to a lesser extent PD-L2 proteins were expressed by non-malignant cells within the microenvironment in non-Hodgkin’s lymphomas (NHL).

The data in this study also highlights the difference in frequency of 9p24.1 alterations and associated expression of PD-1 ligands in specific lymphoid malignancies.

Majority of adverse events (AEs) were drug related and of grade 1 or 2; incidence of severe or life threatening drug related AEs was found to be low across the disease cohorts. Most of the AEs were either managed by treatment with corticosteroids or discontinued due to pneumonitis (grade 2, n=1; grade 3, n=1).

Conclusions

Nivolumab showed encouraging results with a manageable toxicity profile in this population of extensively pre-treated patients with R/R B-cell or T-cell lymphomas. Genetic alterations of PD-L1 and PD-L2 were evaluated and found to be rare among NHLs; which is a stark contrast to the frequent 9p24.1 alterations seen in HLs. Studies involving combinations of nivolumab with rituximab, ipilimumab and other immuno-oncology therapies are currently ongoing to determine whether response rates and duration of response achieved in nivolumab monotherapy can be improved, particularly in B-cell lymphoma subtypes.

Abstract

PURPOSE:

Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies.

METHODS:

In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression.

CONCLUSION:

Nivolumab was well tolerated and exhibited antitumor activity in extensively pre-treated patients with relapsed or refractory B- and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing.

Mar 23, 2017

Apr 25, 2018

Professional society

The European Lymphoma Institute is comprised of a network of top European specialists in the field of lymphoma who are dedicated to research, training and education. Together they look to define strategies to analyse and characterize lymphoma and its common diagnostic procedures and therapeutic standards, as well as to facilitate clinical and fundamental research. This all results in the advancement of lymphoma research and it guarantees equal access for all patients to the best possible care.